1. Field of the Invention
The present invention relates to a method for producing menatetrenone, which is a quinone compound.
2. Description of the Related Art
Menatetrenone is a compound represented by the following formula (1),
and vitamin K2 formulations, which contain this compound as an active ingredient, are used for the prevention and treatment of vitamin K deficiency diseases and are also used as preventive and therapeutic agents for osteoporosis.
Menatetrenone is also present in, for example, fermented soybeans (natto), which is a fermented food, but the industrial methods of menatetrenone production are mainly based on chemical synthesis.
It is known that there are several methods for producing menatetrenone by chemical synthesis. As one example of several methods, it is known that a hydroquinone precursor is oxidized to give menatetrenone, the target quinone (Kozlov, E. I., Meditsinskaya Promyshlennost SSSR (1965), 19(4), 16-21).
The method disclosed in Kozlov uses silver oxide, it is known that there are methods that similarly use metal oxides such as manganese dioxide, lead peroxide (Japanese Patent Application Laid-open No. 49-55650), and so forth.
However, there were drawbacks to the use of metal oxides; for example, the reaction was difficult to control and there was a risk that side reactions would occur. Moreover, the use of metal oxides made it necessary to carry out a post-reaction treatment in order to prevent adverse effects on the environment.
In view the above, it has been developed that a method uses hydrogen peroxide (Japanese Patent Application Laid-open No. 48-49733).
Hydrogen peroxide is, however, a powerful oxidizing agent, and the handling of hydrogen peroxide in large amounts requires special handling with a particular emphasis on safety.
On the other hand, with regard to the production of ubiquinones, which are structurally similar to menatetrenone, it is known that methods use molecular oxygen, which is a milder oxidizing agent (Japanese Patent Publication No. 39-17514 and Japanese Patent Application Laid-open Nos. 52-72884, 54-151932, and 62-81347).
However, it was recognized that when using molecular oxygen in the method for the production of ubiquinones, the reaction rate with oxygen alone was very low and complete oxidation was not to be expected (Japanese Patent Application Laid-open Nos. 54-151932 and 62-81347). In order to overcome this problem, it is known that it is essential to add a base (Japanese Patent Application Laid-open No. 52-72884), silica gel (Japanese Patent Application Laid-open No. 54-151932), or copper or copper ion and ammonia or ammonium ion (Japanese Patent Application Laid-open No. 62-81347) to the reaction solution. These methods that use an additive in addition to the oxidizing agent have the problems encountered for the aforementioned use of the metal oxide to produce quinone, i.e., a risk of side reactions in the presence of the additive and complexity in post-reaction treatment.
In addition, as methods for producing menatetrenone, a specific method that uses molecular oxygen has heretofore been entirely unknown.